Noble gases having non-zero nuclear spin can be hyperpolarised, i.e. have their polarisation enhanced over the equilibrium polarisation, e.g. by the use of circularly polarised light. Preferred techniques for hyperpolarisation include spin exchange with an optically pumped alkali metal vapour and metastability exchange. Noble gases to which this technique can be applied include 3He and 129Xe. As described by M S Albert et al in U.S. Pat. No. 5,545,396, the technique can be used to prepare hyperpolarised noble gases which can then be administered by inhalation for magnetic resonance imaging of the human body.
It is known that the hyperpolarisation of a noble gas can be transferred to another NMR active species by physical contact. Thus WO 97/37239 (Lawrence Berkeley National Laboratory) describes a method which involves: contacting a sample containing an NMR active nucleus with a hyperpolarised noble gas; scanning the sample using nuclear magnetic resonance spectroscopy, magnetic resonance imaging, or both, in order to detect the NMR active nucleus. WO 98/30918 (Nycomed Imaging AS) relates to ex-vivo dynamic nuclear polarisation (DNP) of the NMR active nuclei of an MR imaging agent by a hyperpolarised gas where the gas is separated from the MR imaging agent prior to administration to the body.
The present invention concerns the hyperpolarisation of one or more NMR active nuclei of compounds involved in an assay. The hyperpolarisationmay be carried out using a variety of techniques, such as polarisation transfer from a noble gas, “Brute force”, DNP (WO 98/58272, Nycomed Imaging AS) and the para hydrogen (p-H2) method, as explained below.
The transfer of hyperpolarisation according to the present invention may be achieved by using a hyperpolarised noble gas, preferably 3He or 129Xe, or a mixture of such gases, to effect nuclear polarisation of an assay reagent comprising at least one NMR active nucleus other than the noble gas. The hyperpolarisation of the assay reagent may also be achieved by using anartificially enriched hyperpolarised noble gas, preferably 3He or 129Xe.
Alternatively, hyperpolarisation may be imparted to atoms of significance in biological systems (e.g. 13C, 15N, 31P, 29Si, 19F and 1H isotopes) by thermodynamic equilibration at very low temperature, suitably below 1K, preferably as close to 0 K as possible, and in the presence of a high magnetic field (“Brute force”).
A further alternative is that hyperpolarisation may be imparted by dynamic nuclear polarisation (DNP). In the solid phase, the material is mixed with a paramagnetic species (DNP agent), for example a transition metal ion such as chromium (V) or manganese (II) and/or a free radical generator or other particles having associated free electrons. The method utilises a moderate or high magnetic field and very low temperature, e.g. by carrying out the conversion in liquid helium and a magnetic field of about 1 T or above.
A further technique for imparting hyperpolarisation is para hydrogen induced polarisation which involves cooling hydrogen to a low temperature, e.g. 20 K or less, to give para hydrogen enriched hydrogen. This enriched hydrogen is then used to hydrogenate an unsaturated target organic molecule (containing NMR active nuclei) imparting a non-thermodynamic spin configuration to the target molecule.